Antigen expression of human eccrine sweat glands

Background:  The proliferating abilities of sweat glands are very limited, so researches on the repair and regeneration of sweat glands are important. First of all, we must find out reliable and specific antigen markers of sweat glands.
Objective:  To investigate the antigen expression of human eccrine sweat glands.
Methods:  The development of eccrine sweat glands was investigated by hematoxylin and eosin staining, and the antigen expression was detected by immunohistochemical techniques.
Results:  Human eccrine sweat glands expressed cytokeratin (CK) 7, CK8, CK14, CK18, CK19 and epithelial membrane antigen (EMA). Carcinoembryonic antigen (CEA) was only expressed in sweat glands in the adult skin. Developing and developed sweat glands all had some cells expressing Ki67 and p63 antigens. Epidermal growth factor (EGF) was mainly localized in the secretory cells and ductal cells. Some myoepithelial cells were also labeled with anti-EGF antibody. In the older fetus, positive staining for EGF was seen in the lumen of the secretory portion. EGF receptor (EGFR) was expressed in the ducts.
Conclusions:  Human eccrine sweat glands express CK7, CK8, CK14, CK18, CK19, CEA, EMA, Ki67, p63, EGF and EGFR. In skin, CEA can be used as a specific immunological marker of sweat glands.     

Comparison of proliferating cells between human adult and fetal eccrine sweat glands

Studies of sweat glands had demonstrated that there were degenerating cells and proliferating cells in the eccrine sweat glands. To compare the differences in the proliferating cells between human adult and fetal eccrine sweat glands, immunostaining of proliferating-associated proliferating cell nuclear antigen (PCNA) and Ki67 nuclear antigen (Ki67) was performed, and the location and the percentage of the positive staining cells were analyzed. The results showed that a few cells of the secretory and ductal portion in both the adult and fetal eccrine sweat glands stained positive with Ki67 and PCNA. The labeling index of PCNA in adult eccrine sweat glands was 34.71 ± 8.37%, while that in the fetal was 62.72 ± 6.54%. The labeling index of PCNA in fetal eccrine sweat glands was higher than that in adult. Myoepithelial cells were negative staining with anti-PCNA antibody in adult eccrine sweat glands, while in the fetal a few myoepithelial cells were positive staining. Labeling index of Ki67 in adult eccrine sweat glands was similar to that in the fetal, ranging from 0.5 to 4.3%. Myoepithelial cells of the adult and fetal eccrine sweat glands both were negative staining with anti-Ki67 antibody. We concluded that the myoepithelial cells had proliferating ability only in fetal eccrine sweat glands, and that the proliferating ability of fetal eccrine sweat glands was stronger than that of the adult. Competing interest statement: The authors declare that they have no competing financial interests.     

Immunohistochemical studies of normal sweat glands, sweat gland tumors and extramammary Paget's disease. I. Immunohistochemical studies of normal sweat glands

Localizations of 18 antigens in normal sweat glands were analyzed. The antigens were roughly classified into 8 antigens: 1) distributed throughout the epithelial cells; 2) localized in whole sweat glands; 3) localized only in the secretory portion of sweat glands; 4) localized only in the inner cells of ductal portion of sweat glands; 5) localized in the myoepithelial cells; 6) localized only in the outer cells of dermal ducts of eccrine glands; 7) localized only seen in some of apocrine glands; 8) seen in the inflamed sweat glands. Based on these findings, I discussed about the forms and meanings of localization of those antigens.     

Immunohistochemistry of GCDFP-24 and zinc alpha2 glycoprotein in benign sweat gland tumors

The immunohistochemical localization of two other proteins that are present in breast gross cystic disease fluid, GCDFP-24 and zinc alpha 2 glycoprotein (Zn2GP), were studied in normal skin and in 41 benign sweat gland tumors. GCDFP-24 was localized to apocrine glands. There was no staining of eccrine glands or ducts. There was positive staining in the following sweat gland tumors: apocrine hidrocystoma (four of five), hidradenoma papilliferum (two of four), syringocystadenoma papilliferum (six of seven), mixed tumor (one of one), and glandular elements of cylindroma (one of four). No staining for GCDFP-24 occurred among the following SGT: eccrine hidrocystoma (two cases), eccrine poroma (three cases), syringoma (eight cases), eccrine spiradenoma (two cases), or clear cell hidradenoma (five cases). Zn2GP was localized to both apocrine glands and eccrine glands. Positive staining was seen in the following SGT: apocrine hidrocystoma (five of five), hidradenoma papilliferum (two of four), syringocystadenoma papilliferum (four of seven), mixed tumor (one of one), cylindroma (one of four), eccrine spiradenoma (two of two), and clear cell hidradenoma (one of five). No staining for Zn2GP was seen in the following SGT: eccrine hidrocystoma (two cases), eccrine poroma (three cases), or syringoma (eight cases). GCDFP-24 appears to be a discriminant of apocrine differentiation and function. Zn2GP was expressed predominantly in tumors of apocrine differentiation. However, it was also expressed in some tumors of eccrine differentiation.     

The secretory clear cell of the eccrine sweat gland as the probable source of excess sweat production in hyperhidrosis

Primary hyperhidrosis is characterized by excessive sweating in palmar, plantar and axillary body regions. Gland hypertrophy and the existence of a third type of sweat gland, the apoeccrine gland, with high fluid transporting capabilities have been suggested as possible causes. This study investigated whether sweat glands were hypertrophied in axillary hyperhidrotic patients and if mechanisms associated with fluid transport were found in all types of axillary sweat glands. The occurrence of apoeccrine sweat glands was also investigated. Axillary skin biopsies from control and hyperhidrosis patients were examined using immunohistochemistry, image analysis and immunofluorescence microscopy. Results showed that glands were not hypertrophied and that only the clear cells in the eccrine glands expressed proteins associated with fluid transport. There was no evidence of the presence of apoeccrine glands in the tissues investigated. Preliminary findings suggest the eccrine gland secretory clear cell as the main source of fluid transport in hyperhidrosis.     

Immunohistochemical study of angiotensin receptors in normal human sweat glands and eccrine poroma

BACKGROUND: Angiotensin II exerts its actions through its specific receptors. However, expression of these receptors has not been determined in sweat glands. OBJECTIVES: To clarify the expression and localization of the angiotensin receptors in normal human sweat glands and eccrine poroma. METHODS: Expression of angiotensin type 1 (AT1) and type 2 (AT2) receptors in normal human eccrine and apocrine sweat glands and 12 cases of eccrine poroma was studied using immunohistochemistry. RESULTS: In eccrine sweat glands, the acrosyringium and the inner surfaces and luminal cells of the intradermal duct showed positive staining with AT1. In apocrine sweat glands, the intraepithelial duct and luminal cells of the intradermal duct showed positive staining with AT1. In 12 cases of eccrine poroma, some of the tumour cells in the tumour strands and cells surrounding the luminal structures stained positively. There were no positive findings with AT2. CONCLUSIONS: Studying AT1 distribution may be useful in understanding the pathophysiology of sweat glands and sweat gland tumours.     

Immunohistochemical detection of carcinoembryonic antigen and protein S-100 in sweat gland tumors

Carcinoembryonic antigen (CEA) and S 100 protein (S 100) have been demonstrated in formalin-fixed paraffin sections of eccrine and apocrine sweat glands, and tumors of the sweat glands, as well as, for comparison, in a variety of tumors deriving from epidermal and follicular structures using the peroxidase-antiperoxidase technique. CEA is detectable, as a membrane antigen, in the normal coil of eccrine sweat glands and in the cytoplasm of luminal cells in eccrine and apocrine sweat ducts up to the horny layer. Nearly all tumors of the sweat glands contain variable amounts of CEA. S 100 is localized in the cytoplasm of eccrine coils and secreted with the sweat. Apparently it is only found in tumors derived from the eccrine and apocrine sweat gland coils. Immunohistochemical demonstration of CEA and S 100 thus facilitates the diagnosis of tumors of the sweat glands and their differentiation from epidermal and follicular tumors.     

First case of congenital idiopathic hypohidrosis in China

A 43-year-old Chinese man presented with generalized hypohidrosis, which he had had since birth, without obvious abnormalities of other skin appendages except a sparse beard and axillary hairs. The sweat test revealed localized sweating on the face, axillae and palms. Histopathologic examination showed that the sweat glands were absent in the forearm and thigh, but some eccrine and apocrine sweat glands were present in the right axilla. S-100 was expressed in the nerve terminals surrounding the acini and ducts of the eccrine sweat glands, while PGP9.5 was positive in the acini of apocrine glands and the nerve terminals surrounding the eccrine glands in the axilla. To our knowledge, this is the first case of congenital idiopathic hypohidrosis in China.     

Detection of fluid secretion of three‐dimensional reconstructed eccrine sweat glands by magnetic resonance imaging

We previously showed three‐dimensional (3D) reconstructed eccrine sweat glands have similar structures as native eccrine sweat glands, but whether the 3D reconstructed sweat glands appropriately secrete fluid is still unknown. In this study, Matrigel‐embedded human eccrine sweat gland cells or Matrigel alone were implanted into the groin subcutis of the nude mice. Ten weeks post‐implantation, images of the subcutaneously formed plugs, as well as footpads of rats, pre‐ and post‐pilocarpine/normal saline (NS) injection were acquired using a fat‐suppressed proton density‐weighted magnetic resonance imaging ( MRI ) sequence at 7.0 T, and the regions of interest (ROIs) in plugs and rat footpads were analysed and graphed. A significant increase in the ROI mean proton intensity occurred in both 3D reconstructed and native eccrine sweat glands after pilocarpine injection. The mean proton intensity had no noticeable changes in ROIs of Matrigel plugs between pre‐ and post‐pilocarpine injection, and in ROIs of rat footpads between pre‐ and post‐NS injection. In conclusion, the 3D reconstructed sweat glands possess fluid secretion, which is detectable by fat‐suppressed proton density‐weighted MRI.     

Ultrastructure of eccrine cystadenoma. A case report

A case of eccrine cystadenoma was studied by electron microscopy. The tumor showed two types of cells, luminal and basal cells. The cells lacked the characteristics of the secretory segment of the sweat glands. The features of the luminal cells are similar to those of the intradermal portion of the eccrine sweat duct. In some areas, the lesion showed features characteristic of apocrine gland structure. Nuclear bodies were very frequent. The ultrastructural findings of eccrine cystadenoma support an origin from the ductal portion of eccrine sweat glands.     

Assessment of cellular proliferation of eccrine acrospiromas and eccrine sweat gland carcinomas by AgNOR counting and immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) and Ki-67

Argyrophil nucleolar organizer regions (AgNORs) were counted and immunostaining using antibodies raised against proliferating cell nuclear antigen (PCNA) and Ki-67 was carried out on eccrine acrospiroma and eccrine sweat gland carcinoma, to determine the malignant potential and prognosis of these tumours. Formalin-fixed and paraffin-embedded tissue specimens surgically excised from 25 patients with eccrine sweat gland carcinoma (20 cases of eccrine porocarcinoma, four cases of ductal sweat gland carcinoma and one case of malignant clear cell hidradenoma) and 25 patients with eccrine acrospiroma (16 cases of eccrine poroma, four cases of poroid hidradenoma and five cases of clear cell hidradenoma) were used. PCNA and Ki-67 labelling indices were categorized semiquantitatively into four grades. Significant differences were noted between eccrine sweat gland carcinoma and eccrine acrospiroma with these three methods (P < 0.01). When a cut-off of 5 was chosen, the AgNOR value distinguished eccrine sweat gland carcinoma from eccrine acrospiroma with high specificity and sensitivity. Moreover, we compared the results of these three methods between stages 1 or 2 (17 cases) and stage 3 (eight cases) eccrine sweat gland carcinomas, and no significant differences were observed. From these findings, these three methods are useful in discriminating malignant from benign lesions of eccrine tumours, but have no value in estimating the aggressiveness of eccrine sweat gland carcinomas.     

Congenital Hemangioma of Eccrine Sweat Glands

Abstract: We present six patients with congenital hemangioma of eccrine sweat glands. In every one the lesion was congenital, clinically angiomatous, painless, and nonsweating, with progressive involution over months. Histotogically all specimens showed many dilated capillaries with prominent endothelial cells associated with trie eccrine sweat gland coils.     

Coexistence of Subepidermal Calcified Nodule and Keratosis Punctata in a Patient with Hyperhidrosis

A 47-year-old female with hyperhidrosis developed multiple subepidermal calcified nodules and keratosis punctata on her palms. Although calcification was not detected on eccrine sweat glands around the calcified mass by histologic examination, it was supposed that the eccrine sweat glands may have played a role in inducing these two lesions in our case.     

Aquagenic pruritus. Water-induced activation of acetylcholinesterase

Four patients with aquagenic pruritus (AP), one patient with polycythemia rubra vera, one patient with cold urticaria, and three normal control volunteers were studied to better understand the pathophysiology of water-induced itching. Punch biopsy specimens were taken before and after water contact; the specimens were immediately frozen, sectioned, and stained histochemically for acetylcholinesterase (AChE) activity. This was localized in the nerve fibers surrounding eccrine sweat glands and was quantified by microspectrophotometry. In AP and polycythemia rubra vera after water exposure a significantly increased AChE activity suggesting acetylcholine release was observed, whereas in the patient with cold urticaria and the controls, a significant decrease was noted. Two related patients with AP had an inherited abnormality of serum cholinesterase, which, however, had no obvious correlation with their particular disease. The proof of AChE activation might support the clinical diagnosis and indicate a hypothetical involvement of eccrine sweat glands in the pathogenesis of AP.     

Isolation of a viable eccrine sweat gland by dispase

Dispase was used to obtain viable eccrine sweat glands from human skin in an intact shape. The full thickness of human skin was soaked in a solution of dispase in Eagle's minimum essential medium at a concentration of 500 units/ml and kept in a refrigerator at 4 degrees C for 24 h. The epidermal sheet with its appendages could then be easily separated from the dermis by lifting the epidermis with fine forceps. Electron-microscopic observation revealed that the eccrine sweat gland was completely separated froM the dermis at the basement membrane zone. The isolated epidermal sheet was scarcely dissociated by mechanical agitation in the presence of Ca2+ and Mg2+ ions. The eccrine sweat gland was cut away from the epidermis by using microscissors under a stereomicroscope. A cell suspension of the isolated eccrine sweat glands was obtained after trypsinization. The cells remained more than 90% viable up to 48 h in the culture medium. The obtained viable eccrine sweat glands will be useful for the study of the biology of sweating.     

Identification of secretory immunoglobulin A in human sweat and sweat glands

Secretory immunoglobulin A (sIgA) plays an important role in local immune defense mechanisms. Although skin is always exposed to external antigens, the role of local immune defenses involving sIgA in the skin has not been adequately studied. In order to evaluate the presence of sIgA in sweat, we have measured the concentration of sIgA in human sweat by enzyme immunoassay and have localized the components of sIgA in the sweat glands of human axillary skin. The concentration of sIgA in sweat was found to be 10 times higher in men than in women (13.0 +/- 0.9 micrograms/ml versus 1.6 +/- 0.9 micrograms/ml). Secretory component (SC) was localized immunohistochemically in protein synthetic organelles, such as the perinuclear spaces and Golgi complex, in cytoplasmic vesicles, and along the external surface membranes of mucous cells on the terminal segment of eccrine sweat glands. IgA and J chain were present in plasma cells in the protein synthetic organelles. The luminal aspects of eccrine sweat ducts also strongly express SC, as well as IgA and J chain. Neither SC, IgA, or J chain were identified in epithelial cells of apocrine sweat glands. These findings are consistent with the theory that J chain complexed with dimeric IgA is synthesized in plasma cells and is transported by SC-mediated endocytosis transfer across mucous cells of eccrine sweat glands and thus into sweat.     

Squamous syringometaplasia in lobular panniculitis and pyoderma gangrenosum

Squamous metaplasia of eccrine sweat glands has been most frequently described in chronic cutaneous ulcerations with associated epidermal hyperplasia. We found examples of the process in skin biopsy specimens from five patients: three had associated lobular panniculitis and two had lesions of pyoderma gangrenosum. The metaplasia was located in the mid-to-deep reticular dermis in all five patients and extended into the superficial subcutis in one. Immunohistochemical stains for CEA and S-100 protein were used to accentuate the relationship of the metaplastic islands with eccrine ducts. It is postulated that necrosis of a portion of the eccrine duct is the stimulus for this process.     

Fucosidosis type 3 with angiokeratoma corporis diffusum

Disseminated angiokeratoma were seen in a 14-year-old Japanese boy with an inherited deficiency for alpha-L-fucosidase. He had gargoylian features, psychomotor retardation, small stature, vertebral changes, pale nail beds, recurrent infections and hypohidrosis in addition to angiokeratoma. In the areas of angiokeratoma, we found thin-walled dilated capillaries in the upper dermis. Several nondistended small blood vessels and eccrine sweat glands of secretory coils and ducts appeared narrowed by swollen epithelial cells with a finely vacuolated cytoplasm. In the pale nail bed, we found thickened dermis without an increased number of blood vessels. Electron microscopic studies showed endothelial cells of dermal capillaries and eccrine sweat gland epithelium were extensively enlarged: their cytoplasm was occupied by numerous electronlucent, membrane-limited vacuoles containing scant, finely granular or electronlucent material. In the myoepithelial cells of sweat gland and in the cytoplasm of Schwann cells, lamellar membrane-bound inclusions were seen.     

Immunolocalization of aquaporin-5 in normal human skin and hypohidrotic skin diseases

Aquaporin (AQP)‐5 has been shown to be expressed in the secretory parts of mouse, rat and horse sweat glands. However, the precise localization of AQP‐5 in normal and diseased human skin has not been fully determined. The aim of the present study was to further clarify the immunolocalization of AQP‐5 in normal human skin and hypohidrotic skin diseases. Normal human scalp skin and biopsies from skin affected by hypohidrotic diseases were analyzed for AQP‐5 and/or dermcidin expression by immunohistochemistry, immunofluorescence and/or immunoelectronmicroscopy. AQP‐5 was expressed on the apical and basolateral plasma membranes of the clear cells in eccrine sweat coils, but not in ductal components or apocrine glands. Numbers of AQP‐5‐positive coils in the secretory part of eccrine sweat glands were decreased in Sjögren’s syndrome, but not in skin affected by idiopathic segmental anhidrosis or idiopathic pure sudomotor failure. AQP‐5 was mostly localized to the plasma membranes of clear cells in the secretory coils of eccrine sweat glands, suggesting that it plays a role in producing the primary sweat fluid.     

The absence of apoeccrine glands in the human axilla has disease pathogenetic implications, including axillary hyperhidrosis

BACKGROUND: The existence of a third type of sweat gland in human axillary skin, the apoeccrine gland, with a capacity to produce much higher sweat output than the eccrine gland, was proposed from examination of microdissected glands. However, previous studies of axillary skin glands did not examine the entire individual glandular structure via serial sections and the markers used to identify the different glands gave conflicting results and, hence, the existence of the apoeccrine gland remains controversial. OBJECTIVES: To investigate human axillary sweat glands by serial section histology and immunofluorescence. METHODS: Human axillary sweat glands were investigated by serial sectioning of paraffin wax-embedded skin samples taken by biopsy from four male and six female volunteers (age range 20-35 years). Sections were examined by light microscopy and immunofluorescence, using antibodies to antigens reported to be markers for discriminating between eccrine and apocrine gland cells: CD15, CD44, S100 and human milk fat globulin. RESULTS: Light microscopy demonstrated that there were hair follicles and a mean +/- SD of 76 +/- 14 sweat glands cm(-2). Eccrine and apocrine glands were found to be present; however, no glands resembling the apoeccrine glands were detected. Both types of sweat gland exhibited signs of being active, with segments of the secretory coils displaying flattened cells and dilated glandular lumina; however, this dilation did not extend to obvious changes in the width of the gland. None of the eccrine glands exhibited evidence of the presence of apocrine cells or vice versa. Immunofluorescence markers were found not to be specific and did not discriminate between the different types of glands or demonstrate the presence of apoeccrine glands. CONCLUSIONS: This is the first time that serial sections of axillary skin have been examined by histology and immunofluorescence. The markers reported to discriminate between apocrine and eccrine glands were found to be nonspecific. No evidence of apoeccrine glands was found either by histology or by immunofluorescence.